Overcoming Tumor-Induced Immune Suppression: From Relieving Inhibition to Providing Costimulation with T Cell Agonists.
Overcoming Tumor-Induced Immune Suppression: From Relieving Inhibition to Providing Costimulation with T Cell Agonists.
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DOI：
10.1007/s40259-018-0277-2
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Redmond WL
中科院分区：
文献类型：
--
作者：
Emerson DA;Redmond WL
T细胞生物学和抗体工程的最新进展为癌症免疫治疗的重大改进打开了大门。靶向抑制T细胞功能的关键受体（如细胞毒性T淋巴细胞抗原4（CTLA-4）和程序性死亡配体1（PD-1））的单克隆抗体的初步成功证明了这种新疗法的效力，突出表现为对曾经被认为无法治愈的转移性癌症的长期完全反应。然而，由于多种因素，包括免疫抑制性肿瘤微环境和癌症的突变负担，只有一部分患者对检查点阻断有反应。新型抗体以及靶向共刺激免疫受体的配体-免疫球蛋白融合蛋白正在临床试验中开发和测试，以进一步增强抗肿瘤免疫应答。这些共刺激受体中的许多在肿瘤坏死因子受体超家族（TNFRSF）中并且在多种免疫细胞类型（包括抑制性细胞）上表达。虽然TNFRSFs通过共同的途径发出信号，但靶向不同受体的结果取决于表达相关受体的细胞类型的功能状态。本文就靶向共刺激免疫治疗的研究现状进行综述。
Recent advancements in T-cell biology and antibody engineering have opened doors to significant improvements in cancer immunotherapy. Initial success with monoclonal antibodies targeting key receptors that inhibit T-cell function such as cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death-ligand 1 (PD-1) have demonstrated the potency of this new class of therapy, highlighted by long-term complete responses for metastatic cancers once thought incurable. However, only a subset of patients responds to checkpoint blockade because of a multitude of factors, including an immunosuppressive tumor microenvironment and the mutational burden of the cancer. Novel antibodies, as well as ligand-immunoglobulin fusion proteins that target costimulatory immune receptors, are being developed and tested in clinical trials to further enhance the anti-tumor immune response. Many of these costimulatory receptors are in the tumor necrosis factor receptor superfamily (TNFRSF) and are expressed on multiple immune cell types, including inhibitory cells. While TNFRSFs signal through common pathways, the outcome of targeting different receptors depends on the functional status of the cell types expressing the relevant receptors. In this review, we discuss the current state of targeted costimulatory immunotherapy.
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影响因子：
3
作者：
通讯作者：
--
影响因子：
4.8
作者：
Haxhinasto, SA;Bishop, GA
通讯作者：
Bishop, GA
影响因子：
64.8
作者：
BRUNET, JF;DENIZOT, F;GOLSTEIN, P
通讯作者：
GOLSTEIN, P
DOI：
10.1084/jem.185.12.2053
发表时间：
1997-06-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Carbone E;Ruggiero G;Terrazzano G;Palomba C;Manzo C;Fontana S;Spits H;Kärre K;Zappacosta S
通讯作者：
Zappacosta S
影响因子：
2.6
作者：
Byrd, John C.;Kipps, Thomas J.;O'Brien, Susan
通讯作者：
O'Brien, Susan